Reflection and Reaction

New vaccines for Japanese encephalitis

Vaccines have been one of the true medical milestones; implementation of vaccines has mitigated uncountable morbidity and mortality from numerous diseases, and has succeeded in eradicating one infectious disease (smallpox) from the globe. Vaccines work by stimulating the immune system to recognize pathogens or toxins and mount a response when challenged by natural infection or exposure. Vaccines have been developed against many infections and toxins resulting in neurologic disease, including bacterial meningitides, various viruses, including rabies virus, varicella-zoster virus, poliovirus, and various arthropod-borne (arbo) viruses. Despite the tremendous benefit afforded by vaccines, the immune stimulus provided by vaccination can rarely result in adverse events, including neurologic serious adverse events. This chapter will review the mechanisms by which vaccines confer immunity to various pathogens and agents, and specifically review vaccines that deal with primarily neurologic infections and illnesses. The chapter will also describe the mechanisms associated with neurologic adverse events following vaccination, and the clinical manifestations of these adverse events, as well as how to report such events to public health authorities.

Japanese encephalitis is the most important epidemic encephalitis in the world, responsible for a higher burden of disability than any other arthropod-borne virus. Twenty-four countries, home to over 2.5 billion people, within Asia and the Western Pacific rim are endemic for Japanese encephalitis. In these countries the burden of disease is mostly on children. The adult population is typically immune following childhood exposure. Although only a minority of people exposed to the virus develop disease, Japanese encephalitis is estimated to be responsible for nearly 70 000 cases and 20 000 deaths annually. Patients develop a febrile illness followed by headache, vomiting, impaired consciousness, and often seizures. A wide range of neurologic abnormalities are observed. Typically 20–30% of patients die, and 30–50% of survivors have severe neuropsychiatric sequelae. There are no proven effective therapies and treatment is supportive; however, Japanese encephalitis can be prevented by vaccination.

Seizures and epilepsy may occur secondarily to a wide range of infectious (parasites, bacteria, viruses, or fungi) and inflammatory diseases of the central nervous system, either as the primary manifestation or as part of a diffuse encephalopathy. The pathogenesis and clinical expression of the seizure disorder vary widely from one disease to another, and even across different types of infection with the same agent. While a myriad of infective agents invading the central nervous system may cause seizures, most frequent causes include cerebral malaria, neurocysticercosis, bacterial meningitis or encephalitis, bacterial abscesses, tuberculosis, viral encephalitis, and cryptococcosis. Seizures may also be associated with inflammatory, noninfectious disorders including Rasmussen encephalitis and neurosarcoidosis. Treatment of seizures associated with infection or inflammation usually involves symptomatic management, including antiepileptic drug therapy, and treatment for the underlying disorder. Recognition of infectious- or inflammatory-related acute or remote symptomatic seizures has important therapeutic and prognostic implications.

Fish are a major component of the aquatic fauna. Like other organisms, fish secrete different kinds of antimicrobial peptides (AMPs), which are positively charged short amino-acid-chain molecules involved in host defense mechanisms. Environmental hazards and the greenhouse effect have led to increased evolution of drug- and vaccine-resistant pathogenic strains, and it is necessary to find new drugs with structural uniqueness to fight them. Aquatic sources contain thousands of fish species, and each secretes AMPs with structural differences which can be used by the pharmaceutical industry in its search for novel drugs to treat drug-resistant pathogens. Not only limited to antimicrobial functions, AMPs possess other desirable characteristics which may be exploited in the near future. In this review, we list fish AMPs available from published reports, and discuss application-oriented functions of these AMPs. Notably, the possibilities of using fish AMPs as antimicrobial agents, vaccine adjuvants, inactivated vaccines, and antitumor agents are discussed in this review.

Viral infections of the central nervous system often result in a spectrum of movement disorders, ranging from slowness and rigidity to hyperkinetic movements such as chorea, ballism, dystonia, and myoclonus. The basal ganglia are especially susceptible to some viruses, because of their intrinsic neurotropism, a predilection of opportunistic infections for the deep gray matter of the brain, and possibly the mounting of an autoimmune response against basal ganglia antigens. Viral encephalitides reviewed here include those caused by the human immunodeficiency virus, influenza A virus, the Flavivirus family (such as West Nile virus, Japanese encephalitis virus), and herpes simplex. Hyperkinetic movement disorders associated with prion diseases will also be discussed. The clinical features, etiology, pathogenesis, diagnosis, and treatment of the underlying infections and ensuing movement disorders will be reviewed.

Despite centuries of control efforts, mosquito-borne diseases are flourishing worldwide. With a disproportionate effect on children and adolescents, these conditions are responsible for substantial global morbidity and mortality. Malaria kills more than 1 million children annually, chiefly in sub-Saharan Africa. Dengue virus has expanded its range over the past several decades, following its principal vector, Aedes aegypti, back into regions from which it was eliminated in the mid-20th century and causing widespread epidemics of hemorrhagic fever. West Nile virus has become endemic throughout the Americas in the past 10 years, while chikungunya virus has emerged in the Indian Ocean basin and mainland Asia to affect millions. Japanese encephalitis virus, too, has expanded its range in the Indian subcontinent and Australasia, mainly affecting young children. Filariasis, on the other hand, is on the retreat, the subject of a global eradication campaign. Efforts to limit the effect of mosquito-borne diseases in endemic areas face the twin challenges of controlling mosquito populations and delivering effective public health interventions. Travelers to areas endemic for mosquito-borne diseases require special advice on mosquito avoidance, immunizations, and malaria prophylaxis.